Abstract
Multiple myeloma (MM) remains incurable despite the abundance of novel drugs. As it has been previously shown, preclinical 2D models fail to predict disease progression due to their inability to simulate the microenvironment of the bone marrow. In this review, we focus on 3D models and present all currently available ex vivo MM models that fulfil certain criteria, such as development of complex 3D environments using patients’ cells and ability to test different drugs in order to assess personalized MM treatment efficacy of various regimens and combinations. We selected models representing the top-notch ex vivo platforms and evaluated them in terms of cost, time-span, and feasibility of the method. Finally, we propose where such a model can be more informative in a patient’s treatment timeline. Overall, advanced 3D preclinical models are very promising as they may eventually offer the opportunity to precisely select the optimal personalized treatment for each MM patient.
Highlights
Multiple myeloma (MM) is a haematological malignancy of the plasma cells (PCs), characterized by the accumulation of clonal plasma cells in the bone marrow (BM) and overproduction of monoclonal immunoglobulins (Igs) [1,2]
After an extensive bibliographical search under the terms “multiple myeloma” and “3D culture” or “ex vivo assay” or “3D platform” or “preclinical model”, we selected publications that fulfilled the following criteria: (a) refer to systems that emulate the BM microenvironment, i.e., they use both MM cells and other cell types and/or substances known to participate and regulate cell interactions in the BM microenvironment; (b) apply to MM cells developed in 3D structures; (c) provide results on at least one drug tested; (d) the outcome is evaluated on the basis of MM cell viability following exposure to the drug(s); and (e) the platforms are developed at a personalized patient-specific level
Having thoroughly examined research data available to date, we show that each platform demonstrates particular advantages either as an overall approach or in specific aspects of BM simulation
Summary
Multiple myeloma (MM) is a haematological malignancy of the plasma cells (PCs), characterized by the accumulation of clonal plasma cells in the bone marrow (BM) and overproduction of monoclonal immunoglobulins (Igs) [1,2]. The BM microenvironment is the primary modulator of both malignant transformation and disease progression, where myeloma cells adhere, proliferate, and migrate [5,6,7]. If MM undergoes clonal evolution and drug resistance, it may progress to plasma cell leukemia, an aggressive BM-independent disease, where aberrant PCs spread into circulation or develop extramedullary plasmatocytoma, where MM cells spread in soft-tissues with adverse clinical outcome [8]. Since the traditional preclinical 2D models have failed to predict disease progression due to their inability to simulate the BM microenvironment, 3D platforms are exploited as they likely mimic ex vivo the in vivo cellular and non-cellular interactions
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